JP2011099106A - Zwitterionic group containing compound from michael-type reaction useful as monomer and macromer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a zwitterion including a biocompatible and haemocompatible adduct, a polymer to be formed from the zwitterion, and a coating process and composition comprising the adduct or polymer produced therefrom. <P>SOLUTION: The zwitterion includes the adduct of formula (I) wherein Z is a zwitterionic group; X is an electron withdrawing group selected from the group consisting of a carbonyl group, a sulfone group, sulfonium salt and phosphonium salt; R is a difunctional organic group; A is O or NR<SP>6</SP>; R<SP>1</SP>and R<SP>2</SP>are independently selected from the group consisting of hydrogen and a 1C-6C alkyl group; R<SP>3</SP>is hydrogen or an organic group; R<SP>4</SP>is an organic group, preferably, an optionally substituted alkyl group, an organopolysiloxane group, an organosilyl group or oligo alkoxyalkyl group. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  Phospholipids are phosphate diester compounds and are found naturally in cell membranes. One of the alcohol residues is generally a glycerol derivative and the other alcohol residue is a derivative of a different alcohol with non-ionic, cationic or anionic functionality. Phospholipids and phospholipid analogues are becoming more and more interesting in that they provide useful properties such as biocompatibility and haemocompatibility, and affect the interaction of biomolecules such as proteins and enzymes with surfaces. Pulling.

  European Patent Application Publication No. 0032622, European Patent Application Publication No. 0157469, European Patent Application Publication No. 0555295, European Patent Application Publication No. 0601041, European Patent Application Publication No. 0593561, European Patent Application Publication No. 00639989, International Publication No. 9416748, and International Publication Our past disclosures such as 9416749 describe various synthetic zwitterionic compounds containing phospholipid analogs and their application to devices that are biocompatible and have blood compatible surfaces. The present invention extends this methodology to novel polymer systems that include monomers and macromers produced by Michael-type addition.

As is well known in the literature, amines undergo a nucleophilic attack on the α, β-unsaturated carbonyl of the acrylate function to give a Michael-type 1,4-adduct. (Recent stereoselective synthetic approaches to -amino acids. Cole, Derek C., Tetrahedron (1994), 50 (32), 9517-82)
This technology is applied to a range of curable coatings (Addition products, radiation-curable surface coating compositions based on the addition products, and their use for wood coating and paper coating, Hintze-Bruning, Horst; Cibura, Klaus; Baltus, Wolfgang, US5792827; High-solids coatings -formulation aspects. Nowak, Michael T USA. High Solids Coat. (1982), 7 (3), 23-8) and resins (Curing agents for liquid epoxy resins, and curable polymer compositions containing them. Shiono, Kenji, Suzuki, Takehiro. JP09291135; A process for preparation of room-temperature-curable resins. Furukawa, Hisao; Kawamura, Jo., EP274112).

In polymer chemistry, for example, various polymer hybrids are produced (Conductive wire coating based on a curable acrylate-modified amine-terminated polyamide. Frihart, Charles R .; Kliwinski, Joseph. WO9724191; A polylactone having amino groups, its preparation, and coating and printing ink compositions containing it.Matsui, Hideki., EP713894; Grafting of amine-functional polymers onto functionalized oxymethylene polymers and the resulting graft polymers themselves.Auerbach, Andrew B .; Broussard, Jerry A .; Yang, Nan L .; Paul, James L. EP 400827), and has been actively used to form dendrimer structures. (Dense star polymers. Tomalia, Donald A .; Dewald, James R. WO8402705)
It can also be used to function compounds containing biologically active amines. (A synthesis of N-substituted -alanines: Michael addition of amines to trimethylsilyl acrylate. Kwiatkowski, Stefan; Jeganathan, Azhwarsamy; Tobin, Thomas; Watt, David S. Maxwell H. Synthesis (1989), Issue 12, 946-9) In European Patent Application 0 933 399, a polysiloxane compound having at least one aminoalkyl substituent on a silicon atom is crosslinked by reaction with a di- or oligo-acrylate compound, optionally in the presence of another acrylic compound. . An example of a substituted acrylic compound that could be embodied is N, N-dimethyl-N-methacryloxyethyl-N- (3-sulfopropyl) -ammonium betaine.

  In some prior art documents, this reaction can be caused by either acrylates or methacrylates, but from the standpoint of reactivity, the literature suggests that the former is generally preferred. This reaction usually proceeds without a catalyst, but some have reported a catalyst that simply promotes 1,4 addition to improve the yield. (Catalysis of the specific Michael addition: the example of acrylate acceptors. Cabral, Jose; Laszlo, Pierre; Mahe, Loic, Montautier, Marie Therese; Randriamahefa, S. Lalatiana., Tetrahedron Lett. (1989), 30 (30), 3969-72)

  The present invention relates to a novel polymer and its production process, a process for coating a surface with the novel polymer, and the composition of the polymer. The present invention also provides a novel prepolymer and its production process.

  Such polymers produce or coat medical devices such as devices that come into contact with blood, contact lenses and intraocular lenses, or other devices that contain proteins or are used in contact with biological fluids. Particularly useful above.

In the present invention, a zwitterion comprising a Michael-type addition having the formula I is provided.

(Where
Z is a zwitterionic group,
X is an electron withdrawing group selected from the group consisting of a carbonyl group, a sulfone group, a sulfonium salt, and a phosphonium salt;
R is linear and branched alkanediyl, alkenediyl, alkynediyl, cycloalkanediyl, cycloalkenediyl, cycloalkynediyl, arylene, alkali-lene, aralkylene, alkoxyarylene, alkoxyalkyl, oligoalkoxyalkyl, mono- and di-alkyl Aminoalkyl N-arylaminoalkyl, N-aryl-N-alkylaminoalkyl,
R ¹ and R ² are independently selected from the group consisting of hydrogen and C _1-6 alkyl;
A is O or NR ⁶ wherein R ⁶ is independently selected from the group consisting of hydrogen and C _1-6 alkyl;
R ³ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-Naminoaryl, acyloxy, acyloxyalkyl, acylaminoalkyl, And N-diacyl-iminoalkyl group, mono- and di-alkylaminocarbonyl, organosilyl, arylaminocarbonyl, aryl (alkyl) aminocarbonyl, And an organosiloxyl group, and any of the above groups substituted with any of the following: reactive group, NHCOOR ⁵ group, wherein R ⁵ is hydrogen, linear and branched Alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylamino Alkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxyalkyl, acylaminoalkyl, and N-diacyl-iminoalkyl groups, hydroxyalkyl, hydroxyalkenyl , Hydroxyalkynyl. Selected from the group consisting of hydroxyaryl, hydroxyalkoxyalkyl, and hydroxy (oligoalkoxy) alkyl], —NHCONR ⁷ R ⁸ groups, wherein R ⁷ and R ⁸ are hydrogen, linear and branched Alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, Arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxyalkyl, acylaminoalkyl, and N-diacyliminoalkyl groups, hydroxyalkyl Kill, hydroxyalkenyl, hydroxyalkynyl. Selected from the group consisting of hydroxyaryl, hydroxyalkoxyalkyl, and hydroxy (oligoalkoxy) alkyl], or polymers,
R ⁴ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl , Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy, acyloxyalkyl, acylamino Alkyl and N-diacyl-iminoalkyl groups, mono- and di-alkylaminocarbonyl, organosilyl, arylaminocarbonyl, aryl (alkyl) aminocarbonyl And an organosiloxyl group, and any of the above groups substituted with any of the following:
Group II

[Wherein R, R ¹ , R ² , R ⁴ , Z, A are the same as those in formula (I)],

Group III

[Wherein A ¹ is O or NR ¹³ {wherein R ¹³ is hydrogen or C _1-6 alkyl}, X ¹ is an electron-withdrawing group selected from carbonyl, sulfonyl, sulfonium, phosphonium groups; ¹² is H or C _1-6 alkyl, R ¹⁰ and R ¹¹ are independently selected from H and C _1-4 alkyl, and R ⁹ is optionally substituted alkyl or aryl], a reactive group, or Polymer. )
In the definitions of R ³ , R ⁴ and any of the following groups, preferably any alkyl group or moiety is C _1-18 alkyl, preferably any alkenyl group or moiety is C _2-18 alkenyl, preferably any The alkynyl group or moiety is also C _2-12 alkenyl, preferably any aryl group or moiety is C _6-24 aryl, preferably any alkaryl group or moiety is C _7-24 alkaryl, preferably any Aralkyl groups or moieties are also C _7-24 aralkyl, preferably any cycloalkyl group or moiety is C _4-24 cycloalkyl, preferably any cycloalkenyl group or moiety is C _5-24 cycloalkenyl, preferably Is any cycloalkynyl Or moiety is a _{C 5-24} cycloalkynyl.

The zwitterionic group Z has the general formula (IV)

(Where
A ² and A ³ may be the same or different and are —O—, —S—, —NH—, or a valence bond, preferably —O—.
W ⁺ is a group comprising an ammonium, phosphonium or sulfonium cation group and a group that binds a cation with an anion, preferably a C _1-12 alkane-diyl group, preferably W ⁺ is It is a group of formulas: -W ¹ -N ⁺ R ¹⁴ ₃ , -W ¹ -P ⁺ R ¹⁵ ₃ , -W ¹ -S ⁺ R ¹⁵ ₂ , or -W ¹ -Het ⁺ [wherein W ¹ is One or more, preferably 2 to 6 carbon atom alkane-diyl, optionally having one or more unsaturated ethylene double or triple bonds, aryl having two substituent atoms (aryl) Ene), alkylene arylene, arylene alkylene, alkylene aryl alkylene, cycloalkanediyl, alkylene cycloalkyl, cycloalkyl alkylene, or alkylene Alkyl alkylene, W ¹ groups include one or more substitutions and / or one or more functional groups optionally a plurality of R ¹⁴ groups may be different even in the same, each represents a hydrogen Or an alkyl of 1 to 4 carbons, preferably methyl or aryl such as phenyl, or two groups of R ¹⁴ together with 5 to 7 atoms attached to nitrogen. An aliphatic heterocyclic ring containing, or three of R ¹⁴ together with the attached nitrogen form a fused ring structure containing 5 to 7 atoms in each ring, One or more of ¹⁴ are optionally substituted with hydrophilic functional groups, and the plurality of R ¹⁵ groups may be the same or different, each being either R ¹⁴ or an OR ¹⁴ group , wherein one R ¹⁴ is that defined above There, Het is an aromatic, nitrogen-containing, phosphorus-containing or sulfur-containing ring, for example pyridine. ]. ]

More preferably, the zwitterion of formula (IV) has the general formula (V):

Wherein the plurality of R ¹⁶ groups may be the same or different, each being hydrogen or alkyl of 1 to 4 carbons;
m is 1 to 4, preferably 2;
Preferably the plurality of R ¹⁶ groups are the same, preferably methyl. )
Alternatively, the zwitterionic group may be a butane group such as sulfo-, carboxy-, phospho-butane (ie, the cation is close to the main chain). The butane group should not have an overall charge and is therefore preferably carboxyl or sulfobutane. In the case of phosphobutane, the phosphate end group must be a diester, i.e. it must be esterified with an alcohol. Such groups have the general formula (IV)

(Where
A4 is a valence bond, —O—, —S—, or —NH—, preferably —O—.
V is a carboxylate, sulfonate, or phosphodiester (monovalent) anion;
R ¹⁷ is a valence bond (along with A ⁴ ) and is —C (O) alkylene- or —C (O) NHalkylene, preferably alkane-diyl, preferably 1-6 in the alkane-diyl chain. With carbon atoms,
The plurality of R18 groups may be the same or different and each is hydrogen or alkyl of 1 to 4 carbon atoms, or 5-7 atoms formed with the R18 group and the nitrogen to which they are attached. A heterocycle of
R ¹⁹ is alkanediyl of 1-20, preferably 1-10, more preferably 1-6 carbon atoms.

One preferred sulfobetaine monomer has the formula (VII)

Wherein the plurality of R ²⁰ groups may be the same or different, each being hydrogen or alkyl of 1 to 4 carbons;
s is 2 to 4.

Preferably, the plurality of R ²⁰ groups are the same, and preferably at least one R ²⁰ group is methyl, more preferably both R ²⁰ groups are methyl. )
Alternatively, the zwitterionic group may be an amino acid form, in which case the alpha carbon atom (to which is attached an amine group and a carboxylic acid group) is joined through a linker to the main chain of the biocompatible polymer. Such groups are represented by the general formula (VIII)

(Where
A ⁵ is a valence bond, —O—, —S—, or —NH—, preferably —O—.
R ²² is a valence bond (optionally together with A ⁵ ) and is alkanediyl, —C (O) alkylene- or —C (O) NHalkylene, preferably alkane-diyl, preferably 1 to 6 carbons. With atoms,
The plurality of R ²¹ groups may be the same or different and each is hydrogen or alkyl of 1 to 4 carbon atoms, preferably methyl, or they are attached to two or three of the R21 groups. A 5-7 atom heterocycle formed with the nitrogen in the ring, or a fused ring with 5-7 atoms in each ring, formed with three R21 groups and the nitrogen atom to which they are attached Structure (fused ring laminated structure).

  Preferably X is a carbonyl group.

  Preferably A is O.

Preferably R ¹ is hydrogen.

Preferably R ² is methyl, or more preferably hydrogen.

Preferably, R is _{C 2-6} - diyl - alkane.

Preferably R ³ is hydrogen or an optionally substituted alkylaminocarboxyl or arylaminocarboxyl.

In preferred embodiments, R ³ is a hydrogen atom or comprises a reactive group. Reactive groups include, for example, groups with sites of unsaturation that can form covalent bonds with ionic groups or other groups or substrates. Alternatively, the reactive group increases the ability of the adduct to physically or chemically adsorb to another group or substrate relative to the ability to physically or chemically adsorb exclusively to the reactive group of the adduct. Is possible.

  Preferred substrates include, for example, silicone, polyurethane, polyalkacrylate, polystyrene, polycarbonate, polyester, and iron (especially a stainless alloy).

  Other groups to which the reactive group can be bonded, physically adsorbed or chemisorbed include, for example, another adduct (I) or polymer formed by polymerization of adduct (I), preferred physical or mechanical Polymers, chemicals, ligands such as enzymes and heparins, and biological molecules.

When R ^{3 comprises a} reactive group, it preferably comprises at least one group selected from the group comprising isocyanate, organosilane, and (meth) acryloyloxy.

Most preferably, the R ³ group containing the reactive group is a cycloalkylaminocarbonyl, arylaminocarbonyl, or alkylaminocarbonyl group containing an isocyanate substituent.

Except for hydrogen, R ⁴ is preferably an organic polysiloxane group, an organic alkoxyalkyl group, an organic silyl group, or a C _8-24 alkyl group.

The organosiloxyl group Y used in the present invention, for example R ⁴ , preferably has the formula (IX).

(In the formula, at least one of R ²³ group, R ²⁴ group, and R ²⁵ group is selected from the group consisting of valence bond, C _1-12 alkanediyl, C _2-12 alkenediyl, C _2-12 alkynediyl. And the remaining groups, R23, R24, and R25 are branched and straight chain C _1-12 alkyl, C _6-15 , respectively, which are covalently bonded to the nitrogen atom of the adduct (I). Aryl, C _6-18 alkaryl, C _6-18 aralkyl, C _2-12 alkenyl, C _2-12 alkynyl, all of which are primary, secondary, or tertiary amine groups, or as defined in claim 1 A unit price independently selected from the group which may be substituted by the group (III), n is 0-300.

  Preferably, (IX) has a molecular weight of 300-20000D, 500-10000, more preferably 1000-7000, most preferably 3000-6000.

Preferably R ²³ and R ²⁵ are selected from methanediyl, ethanediyl, propanediyl and butanediyl, both of which are covalently bonded to the nitrogen atom of the individual adduct (I).

Alternatively, or ⁱⁿ addition to ^{R 23} and ^{R 25} are bonded to both adduct (I), or one or one of R24 groups may comprise ^{-NR 26} ₂ substituents, where each R ²⁶ is independently selected from hydrogen or C _1-6 alkyl and aryl, or a substituent of formula III as defined above.

In a preferred embodiment, the adduct (I) is an adduct having one of the formulas (X) (XI) (XII) (XIII) or (XIV).

Wherein each of the plurality of groups R ²⁷ is independently selected from the group consisting of C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl. Preferably C _1-6 alkyl, most preferably methyl or ethyl,
R ²⁸ or each R ²⁸ is independently selected from the group consisting of C _1-6 alkanediyl, C _2-8 alkenediyl, and C _2-8 alkynediyl, preferably C _1-6 alkanediyl,
R ³¹ is selected from the same group as R ²⁷ or is a group R ²⁸ NH ₂ ;
R ³² is selected from the same group as R ²⁷ , or the group R ²⁸ NH ₂ or the group R ²⁸ NH (CH ₂ ) ₂ COO (CH ₂ ) ₂ Z or the group —R ²⁸ N (CONHR ³ 0) CH ₂ CH ₂ COO (CH ₂ ) ₂ Z,
R ²⁹ is selected from the group consisting of hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _2-6 alkenyl, and C _6-18 alkaryl, preferably hydrogen or C _{1 -4} alkyl,
R ³⁰ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono-, di-, and tri-alkylaminoalkyl, arylaminoalkyl, N-arylN-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy, acyloxyalkyl, Acylaminoalkyl and N-diacyl-iminoalkyl groups, alkylaminocarbonyl, organosilyl, and organosiloxyl groups, and zwitterionic groups Z or isocyanates Selected from the group consisting of the above groups substituted with groups,
n is an integer from 1 to 500;
p is an integer from 1 to 50;
q is an integer from 1 to 500;
r is an integer from 1 to 50;
s is 0 or 1 (preferably 1). )
Formulas (XIII) and (XIV) are represented by [—O—SiR272], [—O—SiR32R28. . . ] And [—O—SiR 31 (R 26...)] Groups are not intended to represent a particular order of the organosiloxane backbone. In fact, these groups are arbitrarily or clearly indicated in the trunk.

Most preferably, all groups R ²⁷ , R ³¹ , R ³² are methyl and R ²⁸ is selected from 1,2-ethanediyl, 1,3-propanediyl, and 1,4-butanediyl.

Alternatively, the adduct according to any one of claims 1 to 8, wherein R ⁴ is a polyoxyalkylene having the formula (XV) and has a molecular weight of 100 to 10,000.

(Where
Each group R ³³ is hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl,
Each R ³⁴ is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl;
R ³⁵ is a valence bond, C _1-6 alkane-diyl, C _6-18 arylene, C _6-18 aralkylene, C _2-6 alkene-diyl, mono-, di-, and tri-alkylaminoalkyl, arylaminoalkyl, arylamino A divalent conjugate selected from the group consisting of aryl, N-aryl-N-alkylaminoalkyl, aminoaryl;
R ³⁶ is a divalent conjugate selected from the same group as R ³⁵ or a monovalent conjugate selected from the same group as R ³³ , wherein the aminoalkyl and aminoaryl groups and the alkyl and aryl groups are claimed. Substituted by a group of general formula (II) (III) as defined in item 1;
a is 0 or an integer ranging from 1 to 10;
b is 0 or an integer ranging from 1 to 500;
The molecular weight of (XV) is 100-10000. )

The plurality of R ³⁴ groups are preferably selected from hydrogen and C _1-4 alkyl, more preferably methyl or hydrogen. That is, one R ³⁴ group is a methyl group and the others can be hydrogen, but most preferably all are hydrogen.

  Preferably group XV has a molecular weight in the range of 50 to 20,000.

In a further preferred embodiment, the adduct has the formula (XVI), (XVII) or (XVIII)

Where
Each group R ³³ is independently selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, and C _6-18 alkaryl,
Each group R ³⁷ is independently selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, and C _6-18 alkaryl,
Each group R ³⁴ is independently selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, and C _6-18 alkaryl,
c is 0 or an integer from 1 to 10,
R ³⁸ is selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl,
Each R ³⁹ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxy Aryl, alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono-, di-, and tri-alkylaminoalkyl, arylaminoalkyl, N-arylN-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy (alkene ), Acyloxyalkyl (including alkeneoxyloxyalkyl), acylaminoalkyl, and N-diacyl-iminoalkyl groups, alkylaminocarbonyl, organosilyl And independently selected from the group consisting of an organosiloxyl group and the above group substituted with a zwitterionic group Z or an isocyanate group.

Preferably each R ³⁴ group is selected from propyl, ethyl, methyl and hydrogen, preferably all are the same, more preferably hydrogen.

^R38 is preferably hydrogen.

One preferred organosilane group R ⁴ , or inferior, R ³ has the general formula (XIX);

(Where
Each R ⁴⁷ is hydrogen, branched and straight chain C _1-12 alkyl, C _6-18 aryl, C _6-18 alkaryl, C _6-18 aralkyl, C _2-12 alkenyl, and C _2-12 alkynyl. Selected from the group consisting of
R ⁴⁰ is selected from the group consisting of valence bond, branched and linear C _1-12 alkanediyl, branched and linear C _2-12 alkenediyl, and branched and linear C _2-12 alkynediyl And
X is the adduct of claim 1 to 8 which is attached to the N atom through R ⁴⁰ (I). )

The present invention further provides a process for producing an adduct that forms a zwitterion comprising a compound having the formula (XXII) by subjecting the compound having the formula (XX) to a Michael-type addition with an amine reagent having the formula (XXI). Provided,

(In the formula (XXII),
Z is a zwitterionic group,
A is O or NR ⁶ (wherein R ⁶ is hydrogen or a C _1-6 alkyl group),
X is an electron withdrawing group selected from the group consisting of a carbonyl group, a sulfone group, a sulfonium salt, and a phosphonium salt;
R is linear and branched alkanediyl, alkenediyl, alkynediyl, cycloalkanediyl, cycloalkenediyl, cycloalkynediyl, arylene, alkali-lene, aralkylene, alkoxyarylene, alkoxyalkylene, oligoalkoxyalkylene, mono- And di-alkylaminoalkylenes, N-arylaminoalkylenes, N-aryl-N-alkylaminoalkylenes,
R ⁴¹ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, hydroxyalkyl, hydroxyaryl, alkoxyaryl, Selected from the group consisting of alkoxyalkyl, oligoalkoxyalkyl, acyloxyalkyl, organosilane, organosiloxane group, all of which are amino, N-alkylamino, N, N-dialkylamino, N-aryl-N-alkylamino , And an N-acylamino group,
R ¹ and R ² are independently selected from hydrogen and a C _1-12 alkyl group. )

R ¹ and R ² are selected from hydrogen or a C ₁ -C ₄ alkyl group, preferably both are hydrogen.
The structure is not intended to indicate that it is actually a trans structure when both R ¹ and R ² are not hydrogen atoms and are not cis around the double bond.

  A, Z, R and X have the same preferred definitions as the adducts of general formula I above.

R ⁴¹ is preferably each group from which the preferred R ⁴ groups described above are derived. Often, R ⁴¹ contains an amino substituent, whereby a secondary amine group can participate in the reaction with a zwitterionic reagent of general formula XX.

One mole of amine reagent can react up to 2 moles of zwitterionic reagent. Alternatively, the main product or by-product amine derived from an amine reagent should be cross-linked to a different group or substrate by either Michael-type addition or an alternative reaction mechanism, such as nucleophilic addition or substitution. Or vice versa. At the same time or after the reaction of the zwitterionic reagent and the amine reagent, the di- or oligo-amine reagent (ie where R ⁴¹ contains one or more amine substituents) can be represented by the general formula (XXVI) and further Michael Addition reactions can occur.

(Where
A ¹ is O or NR ¹³ (R ¹³ is hydrogen or a C _1-6 alkyl group),
X ¹ is an electron withdrawing group selected from a carbonyl, sulfonyl, sulfonium, and phosphonium group;
R ¹² is hydrogen or a C _1-6 alkyl group,
R ¹⁰ and R ¹¹ are independently selected from H and C _1-4 alkyl groups, and R ⁹ is an optionally substituted alkyl or aryl group. )

  Such a reaction proceeds further to convert these amine groups of the amine reagent into groups of general formula III as defined above.

Compound (XXII) undergoes a second reaction with isocyanate reagent (XXIII) to form a compound having formula (XXIV).

Wherein R ⁴² is selected from the group consisting of the following groups: alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl of linear and branched carbon chains , Haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl, di-alkylaminoalkyl, N-aryl-N-alkylaminoalkyl and acyloxy (including alkenoyloxy), acyloxyalkyl (Including alkenoyloxyalkyl), N-diacyliminoalkyl groups, organosilanes and organosilane groups, and any of the above groups substituted with zwitterionic groups Z or isocyanate groups.)

In the formula, R ⁴³ is the same as R ⁴² , or when R ⁴² contains an isocyanate group, the isocyanate group and the second reaction mixture (a compound containing a hydroxyl group, or a main product or a by-product amine group) The corresponding group formed by reaction with a compound having an active hydrogen atom present in the compound.

In a preferred embodiment, R ⁴² comprises an unsaturated bond site and most preferably an isocyanate group or an ethylene group, which is another compound of the general formula (XX), another polymer or group, or the above Can be cross-linked to the substrate defined in Said site of unsaturated bonds may alternatively provide a site where homopolymerization or copolymerization of compound (XXIV) can occur, for example an ethylenically unsaturated group such as alkenoyloxy.

Most preferably, the isocyanate reagent is an isocyanate or diisocyanate, preferably selected from the group consisting of the following groups: C _2-30 aliphatic, C _6-30 aromatic and C _6-20 alicyclic isocyanate or diisocyanate, C _4-30 allyl isocyanate, C _3-30 isocyanate alkyl acrylate, C _5-30 isocyanate alkyl methacrylate, More preferably, allyl isocyanate, dimethyl meta-isopropenyl benzyl isocyanate, isophorone diisocyanate, hexamethylene diisocyanate, meta-tetramethylxylylene diisocyanate.

In the reaction of an amine with a zwitterionic reagent, in a preferred embodiment of the amine reagent, the group R ⁴¹ has the general formula XXV.

Wherein one of the R ⁴⁴ or R ⁴⁵ groups is a valence bond and is a divalent component selected from the group consisting of C _1-12 alkanediyl, C _2-12 alkenediyl, C _2-12 alkynediyl groups. And the remaining groups R ⁴⁴ , R ⁴⁵ , and R ⁴⁶ are straight and branched carbon chain C _1-12 alkyl, C _2-12 alkenyl, C _2-12 alkynyl, C _6-24 alkanyl, Independently selected from the group consisting of allyl and one or more amino, N-alkylamino, N, N-dialkylamino, N-alkyl-N-allylamino or groups that can be substituted with N-allylamino groups A monovalent component,
t is 0 to 300. )

In such embodiments, preferably R ⁴⁴ is a C _2-6 alkanediyl group, each of the R ⁴⁵ groups is a methyl group, and R ⁴⁶ is an amino-substituted C _2-6 alkyl group. , N is in the range of 5-50.

In another preferred embodiment of the process of the present invention, in the amine reagent, R ⁴¹ is a group represented by the formula (XXVI) and having a molecular weight of 100 to 10,000.

Wherein each R ³³ group is independently selected from the group consisting of hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-8 alkenyl. , each of ^{R 34} groups include _{hydrogen, C 1-6 alkyl, C 6-18 aryl, C 6-18 aralkyl,} are independently selected from the group consisting of _{C 6-18} alkaryl and _{C 2-8} ^{alkenyl, R 35} Are valence bonds, C _1-6 alkanediyl, C _6-18 arylene, C _6-18 aralkylene, C _2-6 alkenediyl, mono-, di-, and tri-alkylaminoalkyl, arylaminoalkyl, Selected from the group consisting of arylaminoaryl, N-aryl-N-alkylaminoalkyl, and N-aryl-N-alkylaminoaminoaryl A divalent ^{component, R 47 is} a group similar to ^{R 33,} or an amino-substituted _{C 1-12} alkyl, N- alkylamino, N, N- dialkylamino, N- arylamino, or N- aryl -N -Selected from alkylamino groups;
u is a natural number having a range of 0 or 1 to 10;
v is 0 or a natural number having a range of 1 to 500. )

  The two stages of a suitable reaction may be performed simultaneously and separately. It is advantageous for the two stages to be separate in that after the first stage a pure product can be produced which can be characterized.

  If one component can dissolve the other component, the first step (reaction of zwitterionic reagent with amine reagent) may be carried out in a solventless system. Alternatively, an aqueous or organic solvent may be used. Suitable organic solvents include alcohols (including hydroxyalkyl acrylates or hydroxyalkyl methacrylates), chlorinated hydrocarbons, organic sulfoxides, alkyl amides, and ethers.

  When chemical formula (I) contains an ester bond, one requirement for the Michael addition step is that the solvent in which the reaction occurs is to avoid the possibility that the ester bond in the resulting adduct is transesterified. Choose carefully. Transesterification is an acid or base catalyzed reaction and the basic structure of the secondary amine in the adduct appears to be sufficient to catalyze such conversion. In particular, it has been found that the use of methanol as the reaction solvent results in a Michael adduct that is almost exclusively transesterified to produce the methyl ester of the amine. If isopropyl alcohol is used instead of methanol, only traces of transesterification product are detected and transesterification virtually does not occur. The acidity, nucleophilicity, and steric hindrance of the alcohol group are all considerations in determining the suitability of the solvent system used for Michael addition.

  The second stage of the reaction with isocyanate may be carried out in a solventless system or in an aqueous or organic solvent. Suitably, when isocyanates or diisocyanates are used, the reaction is carried out anhydrously. In order for this reaction to proceed, an organic solvent is usually required. Suitable organic solvents include alcohols (including hydroxyalkyl acrylates or hydroxyalkyl methacrylates), chlorinated hydrocarbons, organic sulfoxides, alkyl amides, and ethers.

Particularly suitable solvents for the first reaction are isopropanol or hydroxyethyl methacrylate. Suitable solvents for the second reaction include dimethyl sulfoxide, isopropanol, hydroxyethyl methacrylate, tetrahydrofuran, or N-methylpyrrolidone, or mixtures thereof.

Scheme 1 shows two reaction pathways that result in particularly suitable products.
Here, m and j are integers of 10 to 400.

  In both examples (organosiloxane (B) or polyoxyalkylene (C)), the first two steps may be performed separately or together, depending on the stoichiometry of the reaction. Suitably, the formation of (E) or (H) by the group (A) containing zwitterions occurs in one step. The reaction product is preferably recovered and a further stage reaction with the reactive group (isocyanate in the example shown) is carried out.

For example, when a diisocyanate compound is used to functionalize compound (E) or compound (H), an isocyanate-functional oligomer is formed that can form a block of segmented polyurethaneurea. Will.

  Scheme 2 illustrates another particularly preferred embodiment of the present invention. Compound (E) (or more generally an intermediate of general formula (XXII)) reacts with a diisocyanate compound to produce a compound of type (K) having an additional isocyanate group. This compound can be further reacted with a capping reagent such as hydroxyethyl methacrylate or t-butylaminoethyl methacrylate to form a methacrylate-terminated oligomer (scheme) ideal for free radical polymerization with other ethylenically unsaturated monomers. It is possible to produce compounds (L) and (M)) in FIG. If Michael adducts containing zwitterions react with isocyanates with unsaturated bonds in some form, the above oligomers can also be formed in one step. Particularly useful are isocyanates such as dimethyl meta-isopropenyl benzyl isocyanate, allyl isocyanate, or methacryloxyethyl isocyanate.

  Alternatively, for example, compound K could react with, for example, homologous or heterogeneous group E before introducing the cap. As another way of adding adducts with the necessary physical and / or chemical properties in the molecule, another amine is (although it may or may not be involved in the Michael addition reaction). ) May be introduced into the reaction with (K). This other amine is generally any diamine as long as the proportion of diisocyanate is adjusted so that the carbon chain of compound (K) extends before capping the molecule. Other amine additions are additions prior to cap addition and may be accompanied by further diisocyanate additions to maintain stoichiometry.

  Substances containing the above-mentioned adducts are particularly useful in medical device production.

  Adducts containing organosiloxanes, ie polymers or copolymers produced by polymerization, are particularly useful for the production of contact lenses and intraocular lenses. These provide high oxygen permeability and biocompatibility in the ocular environment.

  When the amine reagent of general formula (XXI) has a functional group in addition to the functionality of the amine, the adduct formed from the amine reagent can provide a product that can be used as an implantable coating. For example, if the amine reagent contains an additional reactive group such as an alkyl group substituted with an aldehyde or carboxylic acid group, the adduct (or polymer) formed from the amine reagent may contain a lysine component. You may utilize for the transplant with respect to the biological tissue which has. Alternatively, when the amine has an organosilane group such as (XIX) as a functional group, this may be utilized to implant the adduct of the present invention on an organic or inorganic substrate. Such compounds and polymers having an organic silane group exhibit exceptional utility in bonding with metal surfaces.

  The presence of the zwitterionic component in the polymer resulting from the polymerization of the adduct of the present invention improves the biocompatibility of the material compared to non-amphoteric ion-containing analogs. If, for example, it is necessary to produce a biodegradable substance, it can be achieved by incorporating a suitably labile carbon chain extender, the degradation product being a zwitterionic group It is less toxic to living organisms than similar compounds that do not have. Similarly, wear debris from non-degradable implants or contact lenses of such materials are also more dangerous to the living or ocular environment than wear debris of similar materials that do not have zwitterionic groups. Should be low.

  Production of the polymer containing the adduct of the present invention may be accomplished by any known polymerization method. As noted above, polymer formation may be achieved by functionalizing the adduct by incorporating an unsaturated bond site, thus providing an adduct that can be polymerized, for example, by free radicals.

  The present invention further includes compositions comprising the adducts of the present invention, and compositions of polymers produced by polymerization of such adducts.

The following examples illustrate the practice of the present invention.

  PEG represents polyethylene glycol and AEW represents the amine equivalent weight. The molecular weight (Mw) of AMS 162 is 4000 to 5000.

All materials were obtained and purified as described in the examples. (2-Acryloyloxyethyl) -2 ′-(trimethyl-ammoniumethyl) phosphate, ie, an inner salt (acryloyl-phosphorylcholine, APC) is obtained as shown below by Ishihara et al. (Polym. J., 22 ( 3), 335, 1990) was generated by changing the previously described route.

All glassware was completely dried before use. 2-Chloro-2-oxo-1,3,2 dioxaphospholene (CCP, Avocado Chemical Co.) (68.3 g, 0.48 mol, 1.05 equivalent weight) was added to a 250 ml self-equilibrium dropping funnel (self -equilibrating dropping funnel) and dissolved in approximately 50 ml of acetonitrile. Hydroxyethyl acrylate (HEA, Aldrich Chemical Co.) (53 g, 0.46 mol) was equipped with a thermometer (range, −100 ° C. to 50 ° C.), dropping funnel, N ₂ bubbler, and magnetic stirrer. Weighed in a 3 neck 2 liter round bottom flask. HEA was dissolved in 700 ml of acetonitrile and cooled to 0 ° C. using a solvent / CO ₂ bath. While stirring with a stirrer, N, N, N ′, N′-tetramethylenediamine (TMEDA, Aldrich Chemical Co.) (36 g, 0.24 mol, 1.05 equivalent weight) was added, followed by 20 The CCP solution was added dropwise over a period of minutes. When CCP is added, TMEDA. The reaction mixture became cloudy due to the formation of the 2HCl salt. The mixture was left stirring for 2 hours.

TMEDA. 2HCl was filtered under reduced pressure and in N ₂ gas and washed with acetonitrile (approximately 60 ml). A clear light yellow solution was collected in a 2 liter Florentin flask. Before bubbling trimethylamine (TMA, Aldrich Chemical Co.) (81.53, 1.38 mol, 3 equivalent weight) into the solution, the solvent / CO ₂ bath was added during stirring to cool the solution to approximately 0 ° C. It was used. The flask was attached to an air condenser with a balloon at the tip and stirred with a stirrer at 50 ° C. for 16 hours. Next, while stirring with a stirrer at 40 ° C., an excess of TMA was removed under vacuum through a cooling trap with solvent / CO ₂ using an HCl trap. For approximately removal of acetonitrile 300 ml, in a vacuum and under _{N 2,} was obtained by filtration as a white solid product APC.

The weight of the collected product was 93.7 g, and the yield was 73%. ¹ H NMR (in D ₂ O) confirmed the product (N ⁺ (CH ₃ ) ₃ characteristic singlet @ 3.15-3.22 ppm, acrylate double bond @ 5.98-6.02 ppm (doublet) ), 6.19-6.26 ppm (quartet), 6.44-6.48 ppm (doublet)). ³¹ PNMR (in CDCl ₃ ) showed the expected peak @ -0.53 ppm.

Example 1 Preparation of APC (Polyoxyalkyleneamine) Adduct 18.73 g (0.067 mol) of APC was weighed into a 100 ml round bottom flask fitted with a condenser and a magnetic stirrer and placed in an oil bath. placed. To this was added 50 ml of IPA and the solution was stirred to dissolve this solid. 600 Mw of polyoxyalkyleneamine macromonomer (Jeffamine ED600, Huntsman Corp.) (20 g, 0.033 mol) was dissolved in 20 ml of IPA and added to the APC solution, and the mixture was stirred with a stirrer for 16 Reflux for hours. Thereafter, IPA was removed by vacuum distillation to obtain a transparent, yellow and viscous liquid product. The conversion efficiency was almost quantitative (37 g, 97%). ¹ HNMR clearly confirmed the quaternary ammonium group of the head group, but confirmed the disappearance of the acrylate double bond.

Second Example: Preparation of polyurethaneurea based on [1,4 butanediol: polyoxyalkyleneamine: hexamethylene diisocyanate ₂ ] All glassware was completely dried before use. Polyoxyalkyleneamine (8.79 g, 22 mmol) was weighed with 40 ml of DMSO (Aldrich Chemical Co.) into an appropriate volumetric flask attached to the condenser and stirrer, approximately 40% (w / v ) Was generated. This is stirred with a stirrer at 50 ° C. until the adduct is dissolved, followed by 2 equivalent weights of hexamethylene diisocyanate (7.39 g, 44 mmol) and an appropriate amount of an appropriate catalyst (usually 3 drops of stannous octoate) and stirred with a stirrer for 5 minutes to form a prepolymer. Next, butanediol (2.00 g, 22 mmol), a carbon chain extender, was added to the mixture and stirred for 1.5 hours, then the temperature was raised to 100 ° C. over 16 hours. The resulting polymer solution was precipitated into water and the solid was filtered under vacuum. Residual solvent was removed by solvent extraction from the solid. After this, the polymer was dried for at least 24 hours before analysis.

The polymer yield was approximately 79%. ^{By 1} HNMR (d ⁶ DMSO), hexamethylene diisocyanate @ 1.22, 1.32 + 2.94 ppm, 3.91 ppm (doublet), 3.65 ppm (multiplet), urea NH@5.60, 5.74 + 5. There was a peak for 84 ppm (singlet each) and NH@7.06 ppm (doublet) for urethane, confirming the polymer structure.

Also by ^{FTIR, N-H @ 3339cm -1} , C-H @ 2932cm -1, Urethane -CONH- @ 1685cm ^-1, Urea ^-NHCONH- @ 1626cm -1, N-H bending @ ^{1561 cm} -1, C -H ^@ 1258cm _-1, confirming the structure with absorption peaks in _{CH 2 -O-CH 2 @ 1101cm} -1.

Example 3 Preparation of polyurethaneurea based on [1,4 butanediol: (APC: polyoxyalkyleneamine): hexamethylene diisocyanate ₂ ] All glassware was completely dried before use. APC: Polyoxyalkyleneamine (7.5 g, 7.8 mmol) and butanediol (0.7 g, 7.8 mmol) were weighed into an appropriate volumetric flask equipped with a mechanical stirrer. This was stirred at 70 ° C. until the mixture was uniform, then cooled to 50 ° C., followed by the addition of 2 equivalent weights of hexamethylene diisocyanate (2.6 g, 15.4 mmol). When the mixture thickened to form a viscous white gum, 30 ml of DMSO (Aldrich Chemical Co.) was added to form an approximately 40 wt% solution that was stirred at 50 ° C. for 16 hours. . The resulting polymer solution was precipitated in 1 liter of acetone and the precipitated solid was filtered under reduced pressure. Residual solvent was removed by solid Soxhlet extraction. After this, the polymer was dried for at least 24 hours before analysis.

The polymer yield was approximately 59%. ^{By 1} HNMR (d ⁶ DMSO), hexamethylene diisocyanate @ 1.22, 1.37 + 2.94 ppm, PC N ⁺ (CH ₃ ) ₃ groups @ 3.13 ppm (singlet), 3.92 ppm (doublet), 3. A polymer structure having a peak of 68 ppm (multiplet) and urethane NH@7.06 ppm (doublet) was confirmed.

Also by ^{FTIR, N-H @ 3371cm -1} , C-H @ 2934cm -1, Urethane -CONH- @ 1718cm ^-1, Urea ^-NHCONH- @ 1631cm -1, N-H bending ^@ 1538cm -1, C -H ^@ 1240 cm _-1, confirming the structure with absorption peaks in _{CH 2 -O-CH 2 @ 1089cm} -1.

Example 4: Preparation of polyurethaneurea based on [1,4 butanediol: (APC: polyoxyalkyleneamine): dicyclohexylmethane diisocyanate ₂ ] All glassware was completely dried before use. APC: Polyoxyalkyleneamine (7.712 g, 8.0 mmol) and butanediol (0.72 g, 8.0 mmol) were weighed into an appropriate volumetric flask equipped with a mechanical stirrer. This was stirred at 70 ° C. until the mixture was homogeneous and after cooling to 50 ° C., 2 equivalent weights of dicyclohexylmethane diisocyanate (4.0 g, 15.5 mmol) were subsequently added. When the mixture thickened to form a viscous white rubber, 30 ml of NMP (Aldrich Chemical Co.) was added to produce an approximately 40% strength by weight solution that was stirred at 50 ° C. for 16 hours. . The resulting polymer solution was precipitated in 1 liter of acetone and the precipitated solid was filtered under reduced pressure. Residual solvent was removed by solid Soxhlet extraction. After this, the polymer was dried for at least 24 hours before analysis.

The polymer yield was approximately 59%. ^{By 1} H NMR (d ⁶ DMSO), dicyclohexylmethane diisocyanate @ 1.20, 1.44 + 1.75 ppm (multiplet), PC N ⁺ (CH ₃ ) ₃ groups @ 3.14 ppm (singlet), 3.68 ppm (multiple) A polymer structure having a peak of 3.92 ppm (doublet), urea NH@5.78, 5.90 + 6.02 ppm (respectively singlet), and urethane NH@7.00 ppm (doublet) was confirmed.

Also by ^{FTIR, N-H @ 3370cm -1} , C-H @ 2971cm -1, Urethane -CONH- @ 1723cm ^-1, Urea ^-NHCONH- @ 1631cm -1, N-H bending ^@ 1532cm -1, C -H ^@ 1234cm _-1, confirming the structure with absorption peaks in _{CH 2 -O-CH 2 @ 1089cm} -1.

Example 5: Preparation of polyurethaneurea based on [1,4 butanediol: (APC: polyoxyalkyleneamine): diphenylmethane diisocyanate ₂ ] All glassware was dried completely before use. APC: Polyoxyalkyleneamine (5.5 g, 5.7 mmol) and butanediol (0.51 g, 5.7 mmol) were weighed into an appropriate volumetric flask equipped with a mechanical stirrer. This was stirred at 70 ° C. until the mixture was homogeneous and after cooling to 50 ° C., 2 equivalent weights of dicyclohexylmethane diisocyanate (2.85 g, 11.4 mmol) were subsequently added. When the mixture thickened to form a viscous white rubber, 30 ml of NMP (Aldrich Chemical Co.) was added to produce an approximately 40% strength by weight solution that was stirred at 50 ° C. for 16 hours. . The resulting polymer solution was precipitated in 1 liter of acetone and the precipitated solid was filtered under reduced pressure. Residual solvent was removed by solvent extraction from the solid. After this, the polymer was dried for at least 24 hours before analysis.

The polymer yield was approximately 59%. ^{By 1} H NMR (d ⁶ DMSO), N ⁺ (CH ₃ ) ₃ groups of PC @ 3.12 ppm (singlet), 3.76 ppm (multiplet), 4.05 ppm (doublet), NH@5.55 of urea ( Singlet), urethane NH@7.03 ppm (doublet), diphenylmethane diisocyanate @ 7.07 + 7.35 ppm (doublet), and the polymer structure was confirmed.

Also by ^{FTIR, N-H @ 3338cm -1} , C-H @ 2973cm -1, Urethane -CONH- @ 1729cm ^-1, Urea ^-NHCONH- @ 1651cm -1, N-H bending ^@ 1538cm -1, C -H ^@ 1224cm _-1, confirming the structure with absorption peaks in _{CH 2 -O-CH 2 @ 1089cm} -1.

Example 6: Properties of some selected polyurethaneureas based on [carbon chain extender _x : (APC: polyoxyalkyleneamine): diisocyanate _{x + 1} ] The polymer is 2,2,2-trifluoroethanol It was found to be soluble in A solution containing 10 mg ml ⁻¹ containing this polymer was prepared, and used to coat (coat) a PET piece (9 mm × 30 mm) by dipping in the solution at a rate of 3 mm sec− ¹ . After 16 hours of air drying, the coated PET was subjected to a double antibody fibrinogen assay to detect protein adsorption to the strip. Table 1 summarizes the results obtained for the inventive polymers described in Examples 2-5. The bioevaluation results represent the percent decrease in adsorbed protein compared to the protein adsorbed on the uncoated PET control strip.

By including the PC component on the Jeffamine soft segment, the amount of fibrinogen adsorbed on the above coated surface is clearly and significantly reduced compared to the control polyurethaneurea without PC. Will come to do. Thus, the information from this analysis will provide further evidence in addition to existing information that suggests that the PC group will indeed improve the biocompatibility of the substance.

Seventh Embodiment: APC: aminopropyl siloxane - Preparation amine dimethylsiloxane adduct equivalent weight 1000 (AMS-162, Apollo Scientific) having, _20g aminopropyl methyl siloxane (NH 2 0.02 mole fraction) - dimethyl Siloxane copolymer (APDMS) was dissolved in 10 g isopropanol in a suitable flask equipped with a mechanical stirrer, thermometer, and N ₂ feed. A solution of APC (5.6 g, 0.02 mol) dissolved in 16 g isopropanol was added to the APDMS solution and the temperature was raised to a fixed point. The rate analysis of this reaction was performed at different temperatures and was shown to be complete at 20, 40, and 80 minutes at 80, 60, and 40 ° C., respectively. 60 ° C. was chosen as a suitable reaction temperature to reduce the possibility of acrylate homopolymerisation. After 60 minutes at 60 ° C., the product was evaporated to dryness using a rotary evaporator to obtain 26 g of viscous rubber. The disappearance of the HEA acrylate double bond (5.8 (d) /6.1 (q) /6.4 (d)) was confirmed by ¹ HNMR.

Peak assignments (Jeol GSX 400, 3999.9 MHz, CDCl ₃ , ppm) are approximately 0.1 (Si—C H ₃ ), 0.45 (Si—C H ₂ —), 1.50 (Si—CH _2). -C H ₂ -), 2.55 (synthesis _{multiplet, -C H 2 -NH-C H} 2 -), 2.87 (-C H 2 -CO -), 3.71 (-C H 2 - OH), 4.22 (-COO-C H 2 - is).

The 8 (a) Example: adduct of 7 Preparation seventh embodiment of allyl isocyanate adduct of Example a (23 g), mechanical stirrer, thermometer, and a suitable flask equipped with N ₂ supply And dissolved in THF (90 g). To promote dissolution, the flask and contents were heated to 45 ° C. A solution of allyl isocyanate (1.5 g) in THF (3.0 g) was added rapidly. When a slight exotherm was observed and the temperature rose to 60 ° C., this state was maintained for 1 hour. Subsequent FTIR spectroscopy of the liquid did not show a characteristic peak for isocyanate stretching at approximately 2259 cm ⁻¹ . The solvent was evaporated and a very viscous rubber was obtained. ¹ HNMR (in CD ₃ OD) confirmed that the product was the following desired allyl derivative.

That is, (Jeol GSX 400, 399.9 MHz, CDCl ₃ , ppm): about 0.1 (Si—C H ₃ ), 0.46 (Si—C H ₂ —), 1.57 (Si—CH ₂ —) C H ₂ −), 2.59 (—C H ₂ —COO—), 3.08 (b, C H ₂ —N—C H ₂ and CONH—C H ₂ —), 3.30 (N ⁺ ( _{CH 3) 3), 3.49 /} 3.8 / 4.1 / 4.25 (-COOC H 2 C H 2 OP (OO-) OC H 2 C H 2 -N -), 4.22 (- _COO-C H 2 -), is 5.05 / 5.15 / 5.87 (allyl -C _H = C H _2).

Eighth (b) Example: Silicon / APC / AI Macromer 7.4 g of APC was weighed in a 250 milliliter round bottom flask equipped with a stirrer, thermometer, and nitrogen blanket. 18.0 g of iPA solvent was added and the mixture was heated to 60 ° C. APC completely dissolved at approximately 50 ° C. An additional 30 g of AMS 162 was added to wash 7.0 g of iPA. The temperature was held at 60 ° C. for 15 minutes and then increased to a reflux temperature of approximately 80 ° C. After 1 hour at 40 ° C., 2.1 g of allyl isocyanate (AI) (Aldrich) was added to wash 1.4 g of iPA. An exotherm was observed and the mixture was heated to reflux for 1 hour. After cooling, FT-IR spectroscopy confirmed that all isocyanate reactions were accompanied by the disappearance of N = C = O stretching.

Removal of the solvent under reduced pressure gave a highly viscous rubber, and ¹ HNMR analysis of the product then confirmed the expected structure of the adduct.

Ninth Example: Preparation of APC-polydimethylsiloxane using amine-functional PDMS, APC, and unsaturated isocyanate 11.2 g APC (0.04 mol) and hydroxyethyl methacrylate (30.5 g) A flask equipped with a thermometer, mechanical stirrer, and N ₂ blanket was packed. The contents were stirred at room temperature until a clear solution was obtained. Hydroquinone (approximately 0.001 g) was added (to prevent premature polymerization of hydroxyethyl methacrylate), followed by 40 g (0.04 mol) of aminopropylmethylsiloxane dimethylsiloxane copolymer. When the temperature was raised to 60 ° C., the solution became clear after approximately 20 minutes. The reaction was maintained at 60 ° C. for 1 hour. The reaction was cooled to 30 ° C., and 8.0 g (0.04 mol) of dimethyl meta-isopropenyl benzyl isocyanate (m-TMI, Cytec Industries) was added with stirring. This reacts selectively with the by-product amine, not the alcohol group of hydroxyethyl methacrylate. When a slight exotherm was observed and the temperature rose to 55 ° C., this state was maintained for 1 hour. The product was obtained as a 67% solution in hydroxy methacrylate.

10th to 18th Examples: Preparation of APC-polydimethylsiloxane adduct suitable for use as a contact lens compounding component. A suitable macromer was generated using the components described in Table 2.

  The term Cap is used to denote the end-caps group for the product. The usual sequence of reactions is Michael addition followed by cap addition followed by diisocyanates that extend the carbon chain. The term “another amine” is any as long as the proportion of diisocyanate is adjusted so that carbon chain extension is achieved using the “another amine” before performing capping. Diamine may also be used to indicate.

Nineteenth Example: General Method for Contact Lens Preparation and Evaluation Contact lens formulation ingredients (macromer / comonomer / initiator / crosslinker) were placed in a glass vial, The mixture was degassed with N ₂ gas for 10 minutes and then dispensed a known quantity into a polypropylene contact lens mold (giving a lens with approximately 3.0D magnification). Next, the mold was sealed and UV-cured for 1 hour using a Black-Ray longwave UV lamp model 100AP. The lens was taken out of the mold by immersing in high-purity water for 1 hour. These were soaked in a 70:30 solution of water and IPA for 2 hours and in borate buffered saline for an additional hour. The lens was then stored in a buffer bottle. A visual assessment of this lens was performed and recorded.

  Lenses were stored in bottles filled with buffer solution. They were then sterilized by pressure treatment at 120 ° C. for 30 minutes. A visual evaluation of the lens was made and recorded.

The equilibrium water content of the lens was first determined by removing excess (free) water from the lens surface using filter paper. Second, the lens was placed in a Pyrex dish containing drierite, microwaved for 5 minutes at maximum power (800 watts), and reweighed. Here, the EWC was calculated as follows.
EWC (%) = (hydrated weight of lens−dry weight of lens) / hydrated weight of lens × 100%

  The oxygen permeability (Dk) of the lens is determined by Mocon's OptiPerm ™ technology (Mocon / Modern Modern) according to SOP # 70-006 designed to measure the Dk value of hydrophilic contact lens materials. Controls Inc., 55428, Minnesota, USA, Minneapolis, Boone Street North 7500). When preparing a Michael-type adduct using hydroxyethyl methacrylate as a solvent, a solvent in which contact lenses are formed is usually not used. This makes it possible to directly mix lenses based on hydroxyethyl methacrylate, but hydroxyethyl methacrylate is not regenerated from the Michael reaction.

Examples 20-23: Preparation of molded contact lenses using selected adducts from Examples 9-18

Table 4 below shows typical examples of the formed lens characteristics. When hydrated, the lens became transparent and could be formed with a wide range of EWCs. Oxygen permeability could be altered by a higher formulation containing silicon.

The biological properties of the lenses formed from the present invention are also advantageous compared to commercially available hydrogel and silicon hydrogel lenses. The lenses were evaluated using the 280 nm UV detection method (Table 5).

24 Example: APC-trimethoxysilane was gently heated in the preparation N ₂ in the gas as the coating ingredients of the base and the adduct, by stirring, the APC of 11g (0.039 mol) of 50ml Dissolved in IPA. When clear, 6.80 g (0.039 mol) of 3-aminopropyltrimethoxysilane (3-APTMS) was added and the reaction mixture was refluxed for 1 hour. ¹ H and ¹³ C NMR showed conversion to Michael addition. Proton COSY was used for peak assignment.

_{^{1 HNMR (CDCl 3, 400MHz,}} ppm): 0.61 (2H, m, Si-C H 2 -), 1.20 (d, iPA-CH 3 exchanged), 1.60 (2H, m, _{Si-CH 2 -C H 2 -} ), 2.55 (2H, t, C H 2 -COO -), each of 2.60 and _{2.88 (2H, t, C H} 2 -NH-C H 2 ), 3.42 (9H, s, N ⁺ (C H ₃ ) ₃ ), 3.52 (integral value indicates some exchange with iPA, C H ₃ —O—Si), 3.80 (2H, ^{_{b, C H 2 -N + (}} CH 3) 3), 4.10 (2H, b, COO-CH 2 -C H 2 -O-P), 4.21 (m, exchanged iPA (m, _{-C H OH)), 4.24 (} 2H, b, COO-C H 2 -), 4.29 (2H, b, P-O-C H 2 -CH 2 -N + ( CH _{3) 3).} ¹³ CNMR (CDCl _3), the characteristic peak, for example, 172 (C = O), and further supports the assignment of structure with _{^{54.9 (N + (C H 3}} ) 3).

FT-IR results indicate the presence of carbonyl / ester, Si—O—CH ₃ , and Si—O—CH (CH ₃ ) ₂ .

To the cooled IPA solution, 3.29 g of hexamethylene diisocyanate (0.0196 mol) was added and the reaction mixture was refluxed for an additional hour. From FT-IR, the reaction of isocyanate due to the disappearance of the N = C = O stretch at approximately 2230 cm ⁻¹ was confirmed. ^{From 1} H and ¹³ C NMR, an APC-TMS dimer was confirmed.

¹ H NMR (CDCl ₃ , 400 MHz, ppm): 0.55 (2H, m, Si—C H ₂ —), 1.20 (d, exchanged iPA-CH ₃ ), 1.30 (2H, b, _{C H 2 -CH 2 -CH 2 -NHCO} ), 1.48 (2H, b, C H 2 -CH 2 -NHCO), 1.62 (2H, m, Si-CH 2 -C H 2 -), 2.57 (2H, t, C H ₂ —COO—), 3.12 (4H, b, C H ₂ —NH—C H ₂ ), 3.42 (9H, s, N ⁺ (C H ₃ ) _{3), 3.48 (2H, b} , C H 2 -NHCO), 3.52 ( integral value indicates that some exchange with iPA has _{occurred, C H 3 -O-Si)} , 3.80 _{^{(2H, b, C H 2}} -N + (CH 3) 3), 4.05 (2H, b, COO-CH 2 -C H 2 -O-P), 4.21 (m, exchanged iPA (m, -C H OH) ), 4.24 (2H, b, COO-C H 2 -), 4.29 (2H, b, P-O-C H _{^{2 -CH 2 -N + (CH 3}} ) 3). ¹³ CNMR (CDCl _3), the characteristic peak, for example, 172 (C = O), 154 (-NR C ONH -), 54.9 (N + (C H 3) 3), 26.30 and 41 (methylene Further supports the assignment of structures having dimers cross-linked).

25 Example: described in Chapter 24 biological evaluation of the examples coatings based 24th embodiment, the solution 20Mgml ^-1 of APC- trimethoxysilane compound in iPA, at a rate of 3mm sec ^-1 And coated on PET. The PET pieces were air dried for 30 minutes and the coating was cured in an oven at 70 ° C. overnight. Enzyme immunoassay based on fibrinogen analysis was used to evaluate the resist adsorption ability of proteins on coated PET samples. The data in Table 5 show that this coating significantly reduced the amount of fibrinogen adsorbed on the surface compared to the uncoated control.

A similar enzyme immunoassay, indicating the degree of E. coli adhesion to the substrate, was used to examine PET samples coated with the invention of Example 24. This data shows that the adhesion of E. coli on the surface of the coated sample was significantly reduced compared to the control sample.

26 Example: APC-surfactant preparation thermometer, mechanical stirrer, and at three-necked flask equipped with a _{N 2} blanket, the dodecylamine 9.2 g (0.05 mol), 9. Dissolved in 2 g isopropanol. Separately, 14.0 g of APC (0.05 mol) was dissolved in 28 g of isopropanol while heating, and this solution was added to the amine solution. The temperature of the reaction mixture was raised to reflux at 83 ° C. and this state was maintained for 4 hours. This was followed by evaporation of the solvent under reduced pressure to give the product as a waxy solid. This structure was confirmed by ¹ H (known) and ¹³ C NMR.

¹ HNMR (CD ₃ OD, ppm, 400 MHz): 0.9 (triplet, 3H, alkyl chain termination C H ₃ ), 1.3-1.6 (broad, 20H, alkyl chain —C H ₂ —), 2.5-2.7 (multiplet, 4H, —CH ₂ —NH—C H ₂ —), 2.9 (triplet, 2H, —C H ₂ CO—), 3.3 (sharp singlet, 9H , N ⁺ (CH ₃ ) ₃ ), 3.7-4.4 (deshielded -C H ₂ -from APC bridging the methylene group).

12 g of this product was dissolved in 46 g of THF at 40 ° C. A solution of 2.0 g of allyl isocyanate (Aldrich) in 2 g of THF was added. A slight exotherm was observed and the reaction temperature was raised to reflux and maintained for 1 hour. After this, 10 g of ethanol was added and reflux was continued for an additional hour. Thereafter, the solvent was evaporated under reduced pressure to obtain 14.6 g of a waxy solid. This structure was confirmed by ¹ H and ¹³ C NMR.

The presence of an allyl group was confirmed by ¹ HNMR (CD ₃ OD, 400 MHz) (characteristic ABC splitting, 5.75 multiplets, 5.15 4.95% doublets doublets). ¹³ C NMR led to confirmation of allyl groups (115.0 and 137.5), urea linkage (159.6), and ester carbonyl (173.4).

Claims (51)

Zwitterion comprising an adduct having the formula (I).

(Where
Z is a zwitterionic group,
X is an electron withdrawing group selected from the group consisting of a carbonyl group, a sulfone group, a sulfonium salt, and a phosphonium salt;
R is linear and branched alkanediyl, alkenediyl, alkynediyl, cycloalkanediyl, cycloalkenediyl, cycloalkynediyl, arylene, alkali-lene, aralkylene, alkoxyarylene, alkoxyalkyl, oligoalkoxyalkyl, mono- and di- Alkylaminoalkyl N-arylaminoalkyl, N-aryl-N-alkylaminoalkyl,
R ¹ and R ² are independently selected from the group consisting of hydrogen and C _1-6 alkyl;
A is O or NR ⁶ wherein R ⁶ is independently selected from the group consisting of hydrogen and C _1-6 alkyl;
R ³ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy, acyloxyalkyl, acylaminoalkyl N-diacyl-iminoalkyl group, mono- and di-alkylaminocarbonyl, organosilyl, arylaminocarbonyl, aryl (alkyl) aminocarbonyl And organosiloxyl groups, and
Reactive groups,
NHCOOR ⁵ groups, wherein R ⁵ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl , Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxyalkyl, acylaminoalkyl, And N-diacyl-iminoalkyl groups, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, hydroxyalkoxyalkyl, and hydroxy (oligoalkoxy) al Is selected from the group consisting of Le,
—NHCONR ⁷ R ⁸ group wherein R ⁷ and R ⁸ are hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, Alkaryl, aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-ary-N-alkylaminoalkyl, N-aryl-Naminoaryl, acyloxy Alkyl, acylaminoalkyl, and N-diacyl-iminoalkyl groups, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, hydroxyalkoxyalkyl, and hydroxy (oligoal) Carboxymethyl) is selected from the group consisting of any of the above groups substituted with any of selected from the group consisting of alkyl or polymers,
R ⁴ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy, acyloxyalkyl, acylaminoalkyl N-diacyl-iminoalkyl group, mono- and di-alkylaminocarbonyl, organosilyl, arylaminocarbonyl, aryl (alkyl) aminocarbonyl And organosiloxyl groups, and
Group II

[Wherein R, R ¹ , R ² , R ⁴ , Z, A are the same as those in formula (I)], group III

[Wherein A ¹ is O or NR ¹³ (wherein R ¹³ is hydrogen or C _1-6 alkyl), X ¹ is an electron-withdrawing group selected from carbonyl, sulfonyl, sulfonium, phosphonium groups; ¹² is H or C _1-6 alkyl, R ¹⁰ and R ¹¹ are independently selected from H and C _1-4 alkyl, and R ⁹ is optionally substituted alkyl or aryl]
It is selected from the group consisting of any of the above groups substituted with either a reactive group or a polymer. ) The adduct according to claim 1, wherein the zwitterionic group Z has the general formula (IV).

(Where
A ² and A ³ may be the same or different and are —O—, —S—, —NH— or a valence bond, preferably —O—, and W ⁺ represents ammonium. , A phosphonium or sulfonium cation group, and preferably a group that binds a cation with an anion that is a C _1-12 alkanediyl group, preferably W ⁺ is of the formula -W ¹ -N ^{It is a group of +} R ¹⁴ ₃ , -W ¹ -P ⁺ R ¹⁵ ₃ , -W ¹ -S ⁺ R ¹⁵ ₂ , or -W ¹ -Het ⁺ . [Wherein W ¹ has one or more, preferably 2 to 6 carbon alkanediyl, 2 substituted atoms, optionally including one or more unsaturated ethylene double or triple bonds. Aryl (arylene), alkylenearylene, arylenealkylene, or alkylenearylalkylene, cycloalkanediyl, alkylenecycloalkyl, cycloalkylalkylene, or alkylenecycloalkylalkylene, wherein the W ¹ group is optionally one or more substituents And / or comprising one or more functional groups, the plurality of R ¹⁴ groups may be the same or different, each of hydrogen or alkyl of 1 to 4 carbons, preferably methyl or phenyl Or two groups out of R ¹⁴ together with the attached nitrogen atom are 5 to Forming an aliphatic heterocycle containing 7 atoms, or three groups of R ¹⁴ together with the attached nitrogen form a fused ring structure containing 5-7 atoms in each ring One or more of R ¹⁴ is optionally substituted with a hydrophilic functional group, and the plurality of R ¹⁵ groups may be the same or different, each of which is R ¹⁴ or An OR ¹⁴ group, wherein R ¹⁴ is as defined above, and Het is an aromatic, nitrogen-containing, phosphorus-containing, or sulfur-containing ring such as pyridine. ]. ) The adduct according to claim 1 or 2, wherein the zwitterion of formula (IV) has the general formula (V).

Wherein the plurality of R ¹⁶ groups may be the same or different, each being hydrogen or alkyl of 1 to 4 carbons;
m is 1 to 4,
Preferably the plurality of R ¹⁶ groups are the same, preferably methyl. )   The adduct according to any of the preceding claims, wherein X is a carbonyl group.   An adduct according to any preceding claim, wherein A is O. An adduct according to any preceding claim, wherein R ¹ and R ² are independently selected from the group consisting of hydrogen and C ₁ -C ₄ alkyl, preferably both are hydrogen. Adduct according to any preceding claim wherein R ³ is hydrogen. The adduct according to any one of claims 1 to 6, wherein R ³ is an optionally substituted alkylaminocarboxyl or arylaminocarboxyl. The adduct according to any of claims 1 to 6, or 8, wherein R ^{3 comprises a} polymer, a monomer having an unsaturated site, or a functional group capable of forming a covalent bond to a substrate.   The adduct according to claim 9, wherein the functional group is isocyanate, allyl, isopropenyl, or (meth) acryloyloxy. The adduct according to any of the preceding claims, wherein R ⁴ is an organosiloxyl group having a molecular weight of 300 to 20000 D and having the formula (IX).

(In the formula, at least one of R ²³ group, R ²⁴ group, and R ²⁵ group is selected from the group consisting of valence bond, C _1-12 alkanediyl, C _2-12 alkenediyl, C _2-12 alkynediyl. Which are covalently bonded to the nitrogen atom of the adduct (I), and the remaining groups, R ²³ , R ²⁴ and R ²⁵ are branched and straight-chain C _1-12 alkyl, C _6-15 aryl, C _6-18 alkaryl, C _6-18 aralkyl, C _2-12 alkenyl, C _2-12 alkynyl, all of which are primary, secondary, or tertiary amine groups, or claim 1 A unit price independently selected from the group optionally substituted by the defined group (III), n is 0-300. 12. Adduct according to claim 11, wherein R ²³ and R ²⁵ are selected from methanediyl, ethanediyl, propanediyl, both covalently bonded to the nitrogen atom of the adduct (I) here. A plurality of R ²⁴ are independently selected from the group consisting of C _1-6 alkyl groups, preferably C _1-4 alkyl groups, most preferably methyl, preferably the same group. The adduct described. 14. Adduct according to any of claims 11 to 13, having the formula (X) (XI) (XII) (XIII) or (XIV).

Wherein each of the plurality of groups R ²⁷ is independently selected from the group consisting of C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl. Preferably C _1-6 alkyl, most preferably methyl or ethyl,
R ²⁸ or each R ²⁸ is independently selected from the group consisting of C _1-6 alkanediyl, C _2-8 alkenediyl, and C _2-8 alkynediyl, preferably C _1-6 alkanediyl,
R ³¹ is selected from the same group as R ²⁷ or is a group R ²⁸ NH ₂ ;
R ³² is selected from the same group as R ²⁷ , or a group R ²⁸ NH ₂ or a group R ²⁸ NH (CH ₂ ) ₂ COO (CH ₂ ) ₂ Z or a group —R ²⁸ N (CONHR ³⁰ ) CH ₂ CH ₂ COO (CH ₂ ) ₂ Z,
R ²⁹ is selected from the group consisting of hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _2-6 alkenyl, and C _6-18 alkaryl, preferably hydrogen or C _{1 -4} alkyl,
R ³⁰ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono-, di-, and tri-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy (alkene oy Roxy), acyloxyalkyl (including alkenyloxyalkyl), acylaminoalkyl, and N-diacyl-iminoalkyl groups, alkylaminocarbonyl, organosilyl, And an organosiloxyl group, and selected from the group consisting of the above groups substituted with zwitterionic groups Z or isocyanate groups,
n is an integer from 1 to 500;
p is an integer from 1 to 50;
q is an integer from 1 to 500;
r is an integer from 1 to 50;
s is 0 or 1 (preferably 1). ) All radicals ^{R 27, R 31, R 32} is ^{methyl, R 28} is ethane - diyl, propane - diyl, and butane - adduct of claim 14 selected from diyl. The adduct according to any one of claims 1 to 8, wherein R ⁴ is the formula (XV) and has a molecular weight of 100 to 10,000.

(Where
Each group R ³³ is hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl,
R ³⁵ is a valence bond, C _1-6 alkane-diyl, C _6-18 arylene, C _6-18 aralkylene, C _2-6 alkene-diyl, mono-, di-, and tri-alkylaminoalkyl, arylamino A divalent conjugate selected from the group consisting of alkyl, arylaminoaryl, N-arylN-alkylaminoalkyl, N-arylNaminoaryl;
R ³⁶ is a divalent conjugate selected from the same group as R ³⁵ or a monovalent conjugate selected from the same group as R ³³ , wherein the aminoalkyl and aminoaryl groups and the alkyl and aryl groups are claimed. Substituted by a group of general formula (II) (III) as defined in item 1;
a is 0 or an integer ranging from 1 to 10,
b is 0 or an integer ranging from 1 to 500. ) The adduct of claim 16, having the formula (XVI) (XVII) or (XVIII).

(Where
Each group R ³³ is independently selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, and C _6-18 alkaryl;
Each group R ³⁷ is independently selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, and C _6-18 alkaryl;
Each group R ³⁴ is independently selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, and C _6-18 alkaryl;
c is 0 or an integer from 1 to 10,
R ³⁸ is selected from the group comprising hydrogen, C _1-4 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl,
Each R ³⁹ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, alkylaminocarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl , Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono-, di-, and tri-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy (alkene ), Acyloxyalkyl (including alkeneoxyloxyalkyl), acylaminoalkyl, and N-diacyl-iminoalkyl groups, alkylaminocarbonyl, organosilyl And independently selected from the group consisting of an organosiloxyl group and the above group substituted with a zwitterionic group Z or an isocyanate group. ) 9. The adduct according to claims 1 to 8, wherein R ⁴ is an organosilyl group having the general formula (XIX), and X is bonded to the N atom of (I) through R ⁴⁰ .

(Where
Each ^{R 47} is comprised of hydrogen, branched and straight-chain _{C 1-12 alkyl, C 6-18 aryl, C 6-18 alkaryl, C 6-18 aralkyl, C 2-12} alkenyl, and _C2-12 alkynyl Selected from the group,
R ⁴⁰ is selected from the group consisting of valence bond, branched and linear C _1-12 alkanediyl, branched and linear C _2-12 alkenediyl, and branched and linear C _2-12 alkynediyl Is done. ) The adduct of claim 1, wherein R ⁴ is an alkyl group having a substituent of formula (II) as defined in claim 1. An adduct according to claims 1 to 19, comprising
R ³ is
Isocyanate,
NHCOOR ⁶ groups, wherein R ⁶ is hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, Alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxyalkyl, acylaminoalkyl, And N-diacyl-iminoalkyl groups, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, hydroxyalkoxyalkyl, and hydroxy (oligoalkoxy) al Is selected from the group consisting of Le),
—NHCONR ⁷ R ⁸ group, wherein R ⁷ and R ⁸ are hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl , Aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl, aminoalkyl, mono- and di-alkylaminoalkyl, arylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl, acyloxy Alkyl, acylaminoalkyl, and N-diacyl-iminoalkyl groups, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, hydroxyaryl, hydroxyalkoxyalkyl, and hydroxy (oligoamide) Kokishi) is selected from the group consisting of alkyl),
Alternatively, it is alkylaminocarbonyl or arylaminocarbonyl substituted with a polymer. R ³ is alkylaminocarbonyl or allylaminocarbonyl, the group NHCONR ⁷ R ⁸ , wherein R ⁷ is an acyloxy-alkyl group and R ⁸ is hydrogen or R ⁷ is (oligoalkoxy) 21. The adduct of claim 20, wherein the adduct is substituted by an alkyl group, and R ⁸ is hydrogen. Either dissolved in a solvent, dispersing the solution preferably containing an adduct as claimed in any one of claims 1 R ³ comprises a functional group 18. A method for producing an adduct comprising forming a zwitterion comprising a compound having the formula (XXII) by subjecting a zwitterionic reagent having the formula (XX) to a Michael type addition with an amine reagent having the formula (XXI).

(In the formula (XXII),
Z is a zwitterionic group,
A is O or NR ⁶ [wherein R ⁶ is hydrogen or a C _1-6 alkyl group],
X is an electron withdrawing group selected from the group consisting of a carbonyl group, a sulfone group, a sulfonium salt, and a phosphonium salt;
R is linear and branched alkane-diyl, alkene-diyl, alkyne-diyl, cycloalkane-diyl, cycloalkene-diyl, cycloalkyne-diyl, arylene, alkali-lene, aralkylene, alkoxyarylene, alkoxyalkylene, Oligoalkoxyalkylenes, mono- and di-alkylaminoalkylenes, N-arylaminoalkylenes, N-aryl-N-alkylaminoalkylenes,
R ⁴¹ represents hydrogen, linear and branched alkyl, alkenyl, and alkynyl groups, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, hydroxyalkyl, hydroxyaryl, alkoxyaryl, alkoxy Selected from the group consisting of alkyl, oligoalkoxyalkyl, acyloxyalkyl, organosilane, organosiloxane group, all of which are amino, N-alkylamino, N, N-dialkylamino, N-allyl-N-alkylamino, And may be substituted with an N-acylamino group,
R ¹ and R ² are independently selected from hydrogen and a C _1-12 alkyl group. ) R ¹ and ^{R 2} are selected from hydrogen or _C 1 -C ₄ alkyl group, The method of claim 23, which is preferably both hydrogen.   The method according to claim 23 or 24, wherein A is O.   26. A method according to any one of claims 23 to 25, wherein Z is as defined in claim 2 or claim 3.   The method according to any one of 23 to 26, wherein X is C═O. 28. A method according to any of claims 23 to 27, wherein a zwitterion comprising a compound of formula (XXII) undergoes a second reaction with an isocyanate of formula (XXIII) to form a compound having formula (XXIV).

(Where
R ⁴² represents linear and branched alkyl, alkenyl, and alkynyl groups, alkoxycarbonyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloaryl, haloalkyl, aryl, alkaryl, aralkyl, alkoxyaryl, alkoxyalkyl, oligoalkoxyalkyl , Di-alkylaminoalkyl, N-aryl-N-alkylaminoalkyl, N-aryl-N-aminoaryl (including alkenoyloxy), acyloxyalkyl (including alkenoyloxyalkyl), N-diacyliminoalkyl group , Organosilane and organosiloxane groups, and selected from the group consisting of the above groups substituted with zwitterionic groups Z or isocyanate groups. )

(Where
R ⁴³ is either the same as R ^42, when R ⁴² contains an isocyanate group, an isocyanate group is a second reaction mixture (compounds containing zwitterionic compound containing a hydroxy group, or a compound containing a primary or secondary amine groups Or a corresponding group formed by reacting with a compound having an active hydrogen atom present in ) _{Isocyanate, C 2-30 alkyl, C 6-30 aryl, C 6-20} alicyclic of formula (XXIII) - mono - or diisocyanates, allyl isocyanate, isocyanate _C 2 _{C 28,} - alkyl acrylates, _{C 2} - the method of claim 28 selected from the group comprising an isocyanate alkyl methacrylate hydrolase _- C _28.   30. The isocyanate is selected from the group consisting of allyl isocyanate, dimethyl metaisopropenyl benzyl isocyanate, isocyanatoethyl methacrylate, isophorone diisocyanate, hexamethylene diisocyanate, dicyclohexylmethane diisocyanate, and meta-tetramethylxylylene diisocyanate. The method described in 1.   The isocyanate group is a diisocyanate and is present in a molar ratio of 0.5 times or more with respect to the compound containing the zwitterion, and preferably has an isocyanate group that does not react with the compound containing the zwitterion, the first and second mono 31. A method according to claim 29 or 30, wherein the method is selected from di-amines, compounds containing mono- and di-hydroxyl groups, and mixtures thereof and reacts with compounds containing additional active hydrogens simultaneously or sequentially. The compound containing the additional active hydrogen is C _2-24 alkanediamine, mono-, diamine-terminated poly (C ₂ or C ₃ alkylene glycol), C _2-24 alkanediol, N-alkylaminoalkyl acrylate and 32. The method of claim 31, wherein the method is selected from N-alkylaminoalkyl methacrylate, _C2-6 hydroxyalkyl acrylate and _C2-6 hydroxyalkyl acrylate, _C2-6 hydroxyalkyl acrylamide and _C2-6 hydroxyalkyl acrylamide. The method according to any one of the groups ^{R 42} are the claims 23 a organosilyl group of the formula (XXV) 31.

(Where
One of the groups R ⁴⁴ or R ⁴⁵ is a divalent selected from the group consisting of valence bond, C _1-12 alkanediyl, C _2-12 alkenediyl, C _2-12 alkynediyl, and the remaining group R ⁴⁴ , R ⁴⁵ and R ⁴⁶ are independently of linear and branched C _1-12 alkyl, C _2-12 alkenyl, C _2-12 alkynyl, C _6-24 alkanyl, C _6-24 aralkyl, and aryl. Selected monovalent, each of which is substituted by one or more amino, N-alkylamino, N, N-dialkylamino, N-alkylN-arylamino, or N-arylamino groups May be. ) The R ⁴⁴ is C _2-6 alkanediyl, each group R ⁴⁵ is methyl, R ⁴⁶ is an amino substituted C _2-6 alkyl group, and n is in the range of 5 to 50. Method. R ⁴² is a group of the formula (XXVI), The method according to any one of claims 23 to 31 having a molecular weight of 10000 100.

(Where
The group R ³³ is independently selected from the group comprising hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl,
Each group R ³⁴ is independently selected from the group comprising hydrogen, C _1-6 alkyl, C _6-18 aryl, C _6-18 aralkyl, C _6-18 alkaryl, and C _2-6 alkenyl;
R ³⁵ is a valence bond, C _1-6 alkane-diyl, C _6-18 arylene, C _6-18 aralkylene, C _2-6 alkene-diyl, mono-, di-, and tri-alkylaminoalkyl, aryl A divalent selected from the group consisting of aminoalkyl, arylaminoaryl, N-arylN-alkylaminoalkyl, and N-alkylaminoaminoaryl;
R ⁴⁷ is selected from the same group as R ³³ , or C _1-12 alkyl is an amino, N-alkylamino, N, N-dialkylamino, N-arylamino, or N-aryl-N-alkylamino group Is replaced by
u is 0 or an integer ranging from 1 to 10,
v is 0 or an integer in the range of 1 to 500. ) R ⁴¹ is a group of the general formula ^(XIX), The method according to any of claims 23 which joins the N atom through ^{R 40} (XXI) 31.

(Where
Each R ⁴⁷ represents hydrogen, branched and straight chain C _1-4 alkyl, C _6-18 aryl, C _6-18 alkaryl, C _6-18 aralkyl, C _2-12 alkenyl, and C _2-12 alkynyl. Selected from the containing group,
R ⁴⁰ is from valence bond, branched and linear C _1-12 alkane-diyl, linear and branched C _2-12 alkene-diyl, linear and branched C _2-12 alkyne-diyl. Selected from the group consisting of )   The method according to any one of claims 23 to 36, wherein the Michael type addition reaction is carried out in a non-solvent system. The Michael type addition reaction is performed in the presence of a solvent, preferably an organic solvent selected from C _1-8 alcohol, C _1-8 chlorinated hydrocarbon, and ether C _1-8 , preferably secondary _37. A method according to any of claims 23 to 36, which is _C1-8 or a tertiary alcohol.   39. A process according to claim 38, wherein the alcohol is selected from isopropanol, isobutanol, t-butanol, hydroxyethyl methacrylate, preferably isopropanol. A polymer adduct is produced by polymerization of an adduct according to any of claims 1 to polymerize through functional groups on R ³ 21. The polymer according to claim 40 R ³ is produced by homopolymerization or copolymerization of adducts containing ethylenically unsaturated groups.   42. Polymer according to claim 41, produced by a polymerization process selected from free radical, cation, anion and metal catalyzed polymerization, preferably by free radical polymerization.   43. A polymer according to claim 41 or 42, wherein the adduct is copolymerized with an ethylenically unsaturated comonomer. A polyurea or polyurethane containing a reaction with an amine or alcohol monomer having a functional group on R ³ is an isocyanate group, the adduct contains one or more isocyanate groups, and the polymerization comprises one or more dual-functional amines or alcohol monomers 41. The polymer of claim 40 that forms.   23. A surface coating process comprising applying the composition of claim 22 to a polymer or metal surface and curing the composition to leave a hard film on the surface. It said surface, on R ³ adducts conditions in the curing step in which a covalent bond is formed is carried out, according to claim 45 which is functional surface capable of generating at least one covalent bond with a functional group Process.   49. The process of claim 48, wherein the adduct is a polymerizable compound and the curing step comprises polymerizing the adduct. A polymerization process comprising homopolymerization or copolymerization of an adduct having a functional group polymerizable to R ^{3 according} to any one of claims 1 to 21.   44. A product comprising the polymer of any of claims 40 to 43.   50. A product according to claim 49 which is a contact lens. R ⁴ is an organic siloxyl body, preferably aminopropyl methylsiloxane - product according to claim 50 comprising residues of dimethyl siloxane copolymer.